The overall goal of this project is to test and refine a preliminary nursing model of Central Nervous System (CNS) Tissue Damage and Cognitive Impairments following whole brain radiation (RTX) and intrathecal Chemotherapy (IT CTX) in children. Whole brain RTX and IT CTX have contributed to the dramatic improvement in the long-term survival of children with acute lymphoblastic leukemia, brain tumors and those requiring bone marrow transplant for oncologic or immunologic disorders. As more children achieve long-term disease remission, knowledge about damage to CNS tissue and the resulting cognitive impairments associated with whole brain RTX and IT CTX will become increasingly important. The specific aims of this study are to: 1) study early CNS tissue damage following whole brain RTX and IT CTX; 2) study delayed CNS tissue damage following whole brain RTX and IT CTX; 3) investigate the cognitive impairments that occur following delayed CNS tissue damage; 4) investigate the relationship between delayed CNS tissue damage and cognitive impairments. A longitudinal, repeated measures design will be used to study 96 children between the ages of 12-months and 12-years. Three different doses of whole brain RTX (2400, 1800 and 1000 centigray) and two different IT CTX regimens (methotrexate (MTX) alone; and MTX, cytosine arabinoside and hydrocortisone) will be studied. Cerebrospinal fluid and serum will be collected prior to and at specific intervals following whole brain RTX and IT CTX to measure membrane damage to the 1) vascular endothelial cells forming the blood brain barrier; 2) myelin (while matter); and 3) brain cells (neural, glial). Cognitive evaluations of general intelligence, visual spatial skills, language and memory will also be conducted. This study will advance nursing knowledge by testing and refining integrated model of CNS tissue damage and Cognitive Impairments. Knowledge about the relationships between tissue damage and cognitive impairments can be used for early identification of children at risk for cognitive impairments so that interventions can be initiated. The findings of this research will be of value to nurses and other health professionals who care for children with whole brain RTX and IT CTX, and may also be applicable to adults who receive similar types of CNS therapy. years have resulted in cure or markedly extended life span for many children. The long-term effects of these treatments, however, have only recent begun to be documented. Cognitive impairment, beginning several years following treatment with whole brain irradiation (RTX) and intrathecal chemotherapy (IT CTX), has been reported, but the mechanisms and pathogenesis of damage are poorly understood. To the extent that it is possible to predict later cognitive impairment on the basis of early CNS damage, and to the extent that damage is found to be dose-related, the proposed investigation will have considerable clinical significance and could lay important groundwork for minimizing CNS effects through radiation dosage adjustments. In addition, the prospective design will facilitate tracking specific cellular and cognitive changes over time to better explain the underlying mechanisms of the impairment.